Process for the production of cyclic diketones

ABSTRACT

The present invention relates to a process for the preparation of compounds of formula (I), wherein the substituents are as defined in claim  1,  by reacting a compound of formula (II), either with a chlorination or bromination agent or with a compound of formula (III) CI—SO 2 R 9 , R 9  being C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, phenyl or C 1 -C 4 alkyl-substituted phenyl, to form the compound of formula (IV), reacting the compound of formula (IV) with a compound of formula (V) M + -O − —C(O)—Y wherein Y is as defined above and M +  is the hydrogen cation or an alkali metal ion, alkaline earth metal ion or ammonium ion, to form the compound of formula (VI) and treating that compound with a cyanide source in the presence of a base.

This application is a 371 of International Application No.PCT/EP2005/004681 filed Apr. 29, 2005, which claims priority to CH00765/04 filed April 30, 2004, the contents of which are incorporatedherein by reference.

The present invention relates to a process for the preparation of cyclic1,3-diketone derivatives carbonylated in the 2-position.

Processes for the preparation of cyclic 1,3-diketones substituted in the2-position by an arylcarbonyl group are described, for example, inWO/0015615, WO 00/37437, WO 01/66522 and WO 01/94339. The compoundsdisclosed therein have herbicidal action.

According to WO 01/94339, such cyclic 1,3-diketones can be prepared by

-   a) reacting a compound of formula A

wherein Y₁ is a leaving group such as, for example, halogen or cyano andR is an organic substituent, in an inert, organic solvent, in thepresence of a base, with a cyclohexanedione of formula B

wherein R is an organic substituent, to form compounds of formula C

and then isomerising those compounds, for example in the presence of abase and a catalytic amount of dimethylaminopyridine or a cyanidesource.

However, such processes have the disadvantage that, in order to preparethe starting compounds of formula A from the acid on which they arebased, an additional activation step is required for introduction of theleaving group. A further problem in the preparation of the compound offormula A is the instability of the starting compounds and theinstability of the compound of formula A itself, which frequently makesthe reaction procedure difficult. This is a serious disadvantageespecially for large-scale production.

The problem of the present invention is accordingly to make available anovel general process for the preparation of monocyclic and bicyclic1,3-diketones which makes it possible to prepare such compounds in highyields and good quality with a simple reaction procedure and littleoutlay without the above-mentioned disadvantages of the known processes.

The present invention accordingly relates to a process for thepreparation of compounds of formula I

wherein Y is an organic substituent which is so selected that thecompound of formula I has a pK value of from 1 to 5;

-   A₁ is CR₁R₂;-   A₂ is oxygen, C(O), SO₂ or (CR₃R₄)_(n);-   n is 1 or 2;-   A₃ is CR₅R₆;-   R₁, R₂, R₃, R₄, R₅ and R₆ are each independently of the others    C₁-C₄alkyl which may mono-, di- or tri-substituted by C₁-C₄alkoxy,    halogen, hydroxy, cyano, hydroxycarbonyl, C₁-C₄alkoxycarbonyl,    C₁-C₄alkylthio, C₁-C₄alkylsulfinyl, C₁-C₄alkylsulfonyl,    C₁-C₄alkylcarbonyl, phenyl or by heteroaryl, it being possible for    the phenyl and heteroaryl groups in turn to be mono-, di- or    tri-substituted by C₁-C₄alkoxy, halogen, hydroxy, cyano,    hydroxycarbonyl, C₁-C₄alkoxycarbonyl, C₁-C₄alkylsulfonyl or by    C₁-C₄haloalkyl, the substituents on the nitrogen in the heterocyclic    ring being other than halogen; and/or R₁, R₂, R₃, R₄, R₅ and R₆ are    each independently of the others hydrogen, C₁-C₄alkoxy, halogen,    hydroxy, cyano, hydroxycarbonyl, C₁-C₄alkoxycarbonyl,    C₁-C₄alkylthio, C₁-C₄alkylsulfinyl, C₁-C₄alkylsulfonyl,    C₁-C₄alkylcarbonyl, phenyl or heteroaryl, it being possible for the    phenyl and heteroaryl groups in turn to be mono-, di- or    tri-substituted by C₁-C₄alkoxy, halogen, hydroxy, cyano,    hydroxycarbonyl, C₁-C₄alkoxycarbonyl, C₁-C₄alkylsulfonyl or by    C₁-C₄haloalkyl, the substituents on the nitrogen in the heterocyclic    ring being other than halogen; and/or-   R₁ and R₂ together form a 3- to 5-membered carbocyclic ring which    may be substituted by C₁-C₄alkyl and/or interrupted by oxygen,    sulfur, S(O), SO₂, OC(O), NR₇ or by C(O); and/or-   R₂ and R₄ together or R₂ and R₅ together form a C₁-C₃alkylene chain    which may be interrupted by oxygen, sulfur, SO, SO₂, OC(O), NR₈ or    by C(O); it being possible for that C₁-C₃alkylene chain in turn to    be substituted by C₁-C₄alkyl; and-   R₇ and R₈ are each independently of the other C₁-C₄alkyl,    C₁-C₄haloalkyl, C₁-C₄alkyl C₁-C₄alkylcarbonyl or    C₁-C₄alkoxycarbonyl; in which process-   a) a compound of formula II

wherein A₁, A₂ and A₃ are as defined for formula I, is reacted, in thepresence of a water-immiscible solvent, in the presence of a base or acatalytic amount of a tertiary amide, either with a chlorination orbromination agent or with a compound of formula IIICl—SO₂R₉  (III),wherein R₉ is C₁-C₄alkyl, C₁-C₄haloalkyl, phenyl orC₁-C₄alkyl-substituted phenyl, to form the compound of formula IV

wherein A₁, A₂ and A₃ are as defined for formula I and Z₁ is chlorine,bromine or OSO₂R₉, R₉ being as defined hereinbefore;

-   b) the compound of formula IV is converted, using a compound of    formula V    M⁺-O⁻—C(O)—Y  (V),    wherein Y is as defined hereinbefore and M⁺ is the hydrogen cation    or an alkali metal ion, alkaline earth metal ion or ammonium ion,    preferably hydrogen, the sodium ion or ammonium ion, into the    compound of formula VI

and

-   c) then the compound of formula VI is treated with a cyanide source    in the presence of a base.

The organic substituent Y may be a substituent of any desired structureprovided that it remains substantially inert under the reactionconditions of the process according to the invention.

Y is preferably a mono-, di- or tri-substituted phenyl, pyridyl orheteroaryl group, especially a di- or tri-substituted phenyl group or adi-substituted 2-pyridyl or 3-pyridyl group, the substitution pattern ofthose groups being freely selectable provided that the groups remainsubstantially inert under the reaction conditions of the processaccording to the invention. Preference is given to phenyl, 3-pyridyl andheteroaryl groups which carry at least one substituent located, veryespecially, in the ortho position.

Especially advantageously, it is possible, using the process accordingto the invention, to prepare compounds of formula I wherein

-   Y is

wherein

-   A₄ is CRa₁ or ═N—(O)_(p);-   p is 0 or 1;-   Ra₁ is hydrogen, C₁-C₆alkyl, hydroxy, C₁-C₆alkoxy, C₁-C₆haloalkoxy,    C₃-C₆alkenyloxy, C₃-C₆haloalkenyloxy, C₃-C₆alkynyloxy,    C₁-C₄alkylcarbonyloxy, C₁-C₄alkylsulfonyloxy, phenylsulfonyloxy,    C₁-C₆alkylthio, C₁-C₆alkylsulfinyl, C₁-C₆alkylsulfonyl,    C₁-C₆alkylamino, di(C₁-C₆alkyl)amino, C₁-C₃alkoxy-C₁-C₃alkylamino,    C₁-C₃alkoxy-C₁-C₃alkyl-N(C₁-C₃alkyl)-, C₁-C₄alkoxycarbonyl,    C₁-C₆haloalkyl, formyl, cyano, halogen, phenyl or phenoxy, it being    possible for the phenyl-containing groups in turn to be substituted    by C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy,    halogen, cyano or by nitro;-   or Ra₁ is a three- to ten-membered monocyclic or together with Ra₂    or Ra₅ annellated bicyclic ring system which may be interrupted once    or up to three times by heterocyclic substituents selected from    oxygen, sulfur, S(O), SO₂, N(Ra₆), carbonyl and C(═NORa₇), the ring    system, unless it is annellated, being bonded to the carbon atom of    the substituent A₄ either directly or by way of a C₁-C₄alkylene,    C₁-C₄alkenylene or C₂-C₄alkynylene bridge which may be interrupted    by oxygen, —N(C₁-C₄alkyl)-, sulfur, sulfinyl or by sulfonyl, and the    ring system may contain not more than 2 oxygen atoms and not more    than two sulfur atoms, and the ring system may in turn be mono-, di-    or tri-substituted by C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl,    C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₁-C₆alkoxy,    C₃-C₆alkenyloxy, C₃-C₆alkynyloxy, C₁-C₆alkylthio,    C₁-C₆haloalkylthio, C₃-C₆akenylthio, C₃-C₆haloalkenylthio,    C₃-C₆alkynylthio, C₁-C₄alkoxy-C₁-C₂alkylthio, C₁-C₄-C₂alkylthio,    C₁-C₄alkoxycarbonyl-C₁-C₂alkylthio, cyano-C₁-C₄alkylthio,    C₁-C₆alkylsulfinyl, C₁-C₆haloalkylsulfinyl, C₁-C₆alkylsulfonyl,    C₁-C₆haloalkylsulfonyl, aminosulfonyl, C₁-C₄alkylaminosulfonyl,    di(C₁-C₄alkyl)aminosulfonyl, di(C₁-C₄alkyl)amino, halogen, cyano,    nitro, phenyl, benzyloxy and/or by benzylthio, and it being possible    for the phenyl-containing groups in turn to be substituted on the    phenyl ring by C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy,    C₁-C₃haloalkoxy, halogen, cyano or by nitro, and substituents on the    nitrogen in the heterocyclic ring are other than halogen;-   or Ra₁ is the group -X₅-X₇ or the group -X₆-X₅-X₇; wherein-   X₅ is oxygen, —O(CO)—, —(CO)O—, —O(CO)O—, —N(C₁-C₄alkyl)—O—,    —O—N(C₁-C₄alkyl)-, sulfur, sulfinyl, sulfonyl, —SO₂N(C₁-C₄alkyl)-,    —N(C₁-C₄alkyl)SO₂—, —N(C₁-C₂alkoxy-C₁-C₂alkyl)SO₂— or    —N(C₁-C₄alkyl)-;-   X₆ is a C₁-C₆alkylene, C₃-C₆alkenylene or C₃-C₆alkynylene chain    which may be mono- or poly-substituted by halogen or by X₈, the    unsaturated bonds of the chain not being bonded directly to the    substituent X₅;-   Ra₆ is hydrogen, C₁-C₄alkyl, C₁-C₄alkylthio-C₁-C₄alkylcarbonyl,    C₁-C₄alkylsulfinyl-C₁-C₄alkylcarbonyl,    C₁-C₄alkylsulfonyl-C₁-C₄alkylcarbonyl, C₁-C₄alkoxycarbonyl,    C₁-C₄alkylcarbonyl, phenylcarbonyl or phenyl, it being possible for    the phenyl groups in turn to be substituted by C₁-C₄alkyl,    C₁-C₄haloalkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy, C₁-C₄alkylcarbonyl,    C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, C₁-C₄alkylthio,    C₁-C₄alkylsulfinyl, C₁-C₄alkyl-SO₂, C₁-C₄alkyl-S(O)₂O,    C₁-C₄haloalkylthio, C₁-C₄haloalkylsulfinyl, C₁-C₄haloalkyl-SO₂,    C₁-C₄haloalkyl-S(O)₂O, C₁-C₄alkyl-S(O)₂NH,    C₁-C₄alkyl-S(O)₂N(C₁-C₄alkyl)-, halogen, nitro or by cyano;-   Ra₇ is hydrogen, C₁-C₄alkyl, C₃-C₄alkenyl, C₃-C₄alkynyl or benzyl;-   Ra₂ is hydrogen, C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl,    C₂-C₆haloalkenyl; vinyl substituted by C₁-C₂alkoxycarbonyl or by    phenyl; or C₂-C₆alkynyl, C₂-C₆haloalkynyl; or ethynyl substituted by    trimethylsilyl, hydroxy, C₁-C₆alkoxy, C₁-C₄alkoxycarbonyl or by    phenyl;-   C₃-C₆allenyl, C₃-C₆cycloalkyl or halo- or    C₁-C₃alkoxymethyl-substituted C₃-C₆cycloalkyl; or-   C₁-C₆alkoxy, C₃-C₆alkenyloxy, C₃-C₆alkynyloxy, C₁-C₆haloalkoxy,    C₃-C₆haloalkenyloxy, cyano-C₁-C₄alkoxy, C₁-C₄alkoxy-C₁-C₄alkoxy,    C₁-C₄alkylthio-C₁-C₄alkoxy, C₁-C₄alkylsulfinyl-C₁-C₄alkoxy,    C₁-C₄alkylsulfonyl-C₁-C₄alkoxy, C₁-C₄alkoxycarbonyl-C₁-C₄alkoxy,    C₁-C₆alkylthio, C₁-C₆alkylsulfinyl, C₁-C₆alkylsulfonyl,    C₁-C₆haloalkylthio, C₁-C₆haloalkylsulfinyl, C₁-C₆haloalkylsulfonyl,    C₁-C₄alkoxycarbonyl-C₁-C₄alkylthio,    C₁-C₄alkoxycarbonyl-C₁-C₄alkylsulfinyl,    C₁-C₄alkoxycarbonyl-C₁-C₄alkylsulfonyl, C₁-C₆alkylamino,    di(C₁-C₆-alkylsulfinyl, C₁-C₃alkoxy-C₁-C₃alkylamino,    C₁-C₃alkoxy-C₁-C₃alkyl-N(C₁-C₃alkyl), C₁-C₆-alkylaminosulfonyl,    di(C₁-C₆alkyl)aminosulfonyl, C₁-C₄alkylsulfonyloxy,    C₁-C₄haloalkylsulfonyloxy, C₁-C₄alkylsulfonylamino,    C₁-C₄alkylsulfonyl-N(C₁-C₄alkyl), cyano, carbamoyl,    C₁-C₄alkoxycarbonyl, formyl, halogen, rhodano, amino,    hydroxy-C₁-C₄alkyl, C₁-C₄alkoxy-C₁-C₄alkyl,    C₁-C₄alkylthio-C₁-C₄alkyl, C₁-C₄alkylsulfinyl-C₁-C₄alkyl,    C₁-C₄alkylsulfonyl-C₁-C₄alkyl, cyano-C₁-C₄alkyl,    C₁-C₆alkylcarbonyloxy-C₁-C₄alkyl, C₁-C₄alkoxycarbonyl-C₁-C₄-alkyl,    C₁-C₄alkoxycarbonyloxy-C₁-C₄alkyl, rhodano-C₁-C₄alkyl,    phenyl-C₁-C₄alkyl, phenoxy-C₁-C₄alkyl, benzyloxy-C₁-C₄alkyl,    benzoyloxy-C₁-C₄alkyl, (2-oxiranyl)-C₁-C₄alkyl,    C₁-C₄alkylamino-C₁-C₄alkyl, di(C₁-C₄alkyl)amino-C₁-C₄alkyl,    C₁-C₁₂alkylthiocarbonyl-C₁-C₄alkyl or formyl-C₁-C₄alkyl, benzylthio,    benzylsulfinyl, benzylsulfonyl, benzyloxy, benzyl, phenyl, phenoxy,    phenylthio, phenylsulfinyl or phenylsulfonyl; it being possible for    the phenyl-containing groups in turn to be substituted by    C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, halogen,    cyano or by nitro; or-   Ra₂ is a three- to ten-membered monocyclic or annellated bicyclic    ring system which may be aromatic, saturated or partially saturated    and may contain from 1 to 4 hetero atoms selected from nitrogen,    oxygen and sulfur, the ring system being bonded to the group Q₁ or    Q₂ directly or by way of a C₁-C₄alkylene, C₁-C₄alkenylene or    C₂-C₄alkynylene bridge which may be interrupted by oxygen,    —N(C₁-C₄alkyl)-, sulfur, sulfinyl, sulfonyl or by carbonyl; and each    ring system may contain not more than 2 oxygen atoms and not more    than two sulfur atoms, and the ring system may in turn be mono-, di-    or tri-substituted by C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl,    C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₁-C₆alkoxy,    C₁-C₆haloalkylthio, C₃-C₆alkenyloxy, C₃-C₆alkynyloxy, hydroxy,    mercapto, C₁-C₆alkylthio, C₁-C₆haloalkylthio, C₃-C₆alkenylthio,    C₃-C₆haloalkenylthio, C₃-C₆alkynylthio, C₁-C₄alkoxy-C₁-C₃alkylthio,    C₁-C₄alkylcarbonyl-C₁-C₃alkylthio,    C₁-C₄alkoxycarbonyl-C₁-C₃alkylthio, cyano-C₁-C₃alkylthio,    C₁-C₆alkylsulfinyl, C₁-C₆haloalkylsulfinyl, C₁-C₆alkylsulfonyl,    C₁-C₆haloalkylsulfonyl, aminosulfonyl, C₁-C₄alkylaminosulfonyl,    di(C₁-C₄alkyl)aminosulfonyl, di(C₁-C₄alkyl)amino, halogen, cyano,    nitro, phenyl and/or by benzylthio; it being possible for phenyl and    benzylthio in turn to be substituted on the phenyl ring by    C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, halogen,    cyano or by nitro, and substituents on the nitrogen in the    heterocyclic ring are other than halogen; or-   Ra₂ is the group -X₁-X₃ or the group -X₂-X₁-X₃; wherein-   X₁ is oxygen, —O(CO)—, —(CO)O—, —O(CO)O—, —N(C₁-C₄alkyl)—O—,    —O—N(C₁-C₄alkyl)-, thio, sulfinyl, sulfonyl, —SO₂N(C₁-C₄alkyl)-,    —N(C₁-C₄alkyl)SO₂—, —N(C₁-C₂alkoxy-C₁-C₂alkyl)SO₂— or    —N(C₁-C₄alkyl)-;-   X₂ is a C₁-C₆alkylene, C₃-C₆alkenylene or C₃-C₆alkynylene chain    which may be mono- or poly-substituted by halogen or by X₄, the    unsaturated bonds of the chain not being bonded directly to the    substituent X₁;-   X₃ and X₇ are each independently of the other a C₁-C₈alkyl,    C₃-C₆alkenyl or C₃-C₆alkynyl group which may be mono-, di- or    tri-substituted by halogen, hydroxy, amino, formyl, nitro, cyano,    mercapto, carbamoyl, C₁-C₆alkoxy, C₁-C₆alkoxycarbonyl, C₂-C₆alkenyl,    C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₃-C₆cycloalkyl or    halo-substituted C₃-C₆cycloalkyl;-   or by C₃-C₆alkenyloxy, C₃-C₆alkynyloxy, C₁-C₆haloalkoxy,    C₃-C₆haloalkenyloxy, cyano-C₁-C₆alkoxy, C₁-C₆alkoxy-C₁-C₆alkoxy,    C₁-C₆alkoxy-C₁-C₆alkoxy-C₁-C₆alkoxy, C₁-C₆alkylthio-C₁-C₆alkoxy,    C₁-C₆alkylsulfinyl-C₁-C₆alkoxy, C₁-C₆alkylsulfonyl-C₁-C₆alkoxy,    C₁-C₆alkoxycarbonyl-C₁-C₆alkoxy, C₁-C₆alkoxycarbonyl,    C₁-C₆alkylcarbonyl, C₁-C₆alkylthio, C₁-C₆alkylsulfinyl,    C₁-C₆alkylsulfonyl, C₁-C₆haloalkylthio, C₁-C₆haloalkylsulfinyl,    C₁-C₆haloalkylsulfonyl; oxiranyl which may in turn be substituted by    C₁-C₆alkyl; (3-oxetanyl)-oxy which may in turn be substituted by    C₁-C₆alkyl; benzyloxy, benzylthio, benzylsulfinyl, benzylsulfonyl,    C₁-C₆alkylamino, di(C₁-C₆alkyl)amino, C₁-C₄alkyl-S(O)₂O—,    di(C₁-C₄alkyl)aminosulfonyl, rhodano, phenyl, phenoxy, phenylthio,    phenylsulfinyl or by phenylsulfonyl; and it being possible for the    phenyl- or benzyl-containing groups in turn to be substituted by one    or more C₁-C₆alkyl, C₁-C₆haloalkyl, C₁-C₆alkoxy, C₁-C₆haloalkoxy,    halogen, cyano, hydroxy or nitro groups; or-   X₃ and X₇ are phenyl which may be mono- or poly-substituted by    C₁-C₆alkyl, C₁-C₆haloalkyl, C₁-C₆alkoxy, C₁-C₆haloalkoxy, halogen,    cyano, hydroxy or by nitro; or-   X₃ and X₇ are each independently of the other C₃-C₆cycloalkyl,    C₁-C₆alkoxy- or C₁-C₆haloalkyl-substituted C₃-C₆cycloalkyl,    3-oxetanyl or C₁-C₆alkyl-substituted 3-oxetanyl; or-   X₃ and X₇ are each independently of the other a three- to    ten-membered monocyclic or annellated bicyclic ring system which may    be aromatic, saturated or partially saturated and may contain from 1    to 4 hetero atoms selected from nitrogen, oxygen and sulfur, the    ring system being bonded to the substituent X₁ or X₅ directly or by    way of a C₁-C₄alkylene, C₂-C₄alkenylene, C₂-C₄alkynylene,    —N(C₁-C₄alkyl)-C₁-C₄alkylene, —S(O)—C₁-C₄alkylene or    —SO₂-C₁-C₄alkylene group, and each ring system may contain not more    than 2 oxygen atoms and not more than two sulfur atoms, and the ring    system may in turn be mono-, di- or tri-substituted by C₁-C₆alkyl,    C₁-C6haloalkyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl, C₂-C₆alkynyl,    C₂-C₆haloalkynyl, C₁-C₆alkoxy, hydroxy, C₁-C₆haloalkoxy,    C₃-C₆alkenyloxy, C₃-C₆alkynyloxy, mercapto, C₁-C₆alkylthio,    C₁-C₆haloalkylthio, C₃-C₆alkenylthio, C₃-C₆haloalkenylthio,    C₃-C₆-alkylthio, C₁-C₃alkoxy-C₁-C₃alkylthio,    C₁-C₄alkylcarbonyl-C₁-C₂alkylthio,    C₁-C₄alkoxycarbonyl-C₁-C₂alkylthio, cyano-C₁-C₃alkylthio,    C₁-C₆alkylsulfinyl, C₁-C₆haloalkylsulfinyl, C₁-C₆alkylsulfonyl,    C₁-C₆haloalkylsulfonyl, aminosulfonyl, C₁-C₂alkylaminosulfonyl,    di(C₁-C₂alkyl)aminosulfonyl, di(C₁-C₄alkyl)amino,    C₁-C₆carbonylamino, halogen, cyano, nitro, phenyl, benzyloxy and/or    by benzylthio, it being possible for the phenyl groups in turn to be    substituted on the phenyl ring by C₁-C₃alkyl, C₁-C₃haloalkyl,    C₁-C₃alkoxy, C₁-C₃haloalkoxy, halogen, cyano or by nitro, and the    substituents on the nitrogen in the heterocyclic ring are other than    halogen; and-   X₄ and X₈ are each independently of the other hydroxy, C₁-C₆alkoxy,    (C₃-C₆cycloalkyl)oxy, C₁-C₆alkoxy-C₁-C₆alkoxy,    C₁-C₆alkoxy-C₁-C₆alkoxy-C₁-C₆alkoxy or C₁-C₆alkylsulfonyloxy;-   Ra₃ is hydrogen, C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl,    C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₃-C₆cycloalkyl,    C₁-C₆alkoxy, C₁-C₆haloalkoxy, C₁-C₆alkylthio, C₁-C₆alkylsulfinyl,    C₁-C₆alkylsulfonyl, C₁-C₆haloalkylthio, C₁-C₆haloalkylsulfinyl,    C₁-C₆haloalkylsulfonyl, amino, C₁-C₆alkylamino, di(C₁-C₆alkyl)amino,    C₁-C₄alkylsulfonyl-N(C₁-C₄alkyl)-, C₁-C₆alkylaminosulfonyl,    di(C₁-C₆alkyl)aminosulfonyl, cyano, halogen, C₁-C₄alkoxy-C₁-C₄alkyl,    C₁-C₄alkylthio-C₁-C₄alkyl, C₁-C₄alkylsulfinyl-C₁-C₄alkyl,    C₁-C₄alkylsulfonyl-C₁-C₄alkyl,phenyl, phenylthio, phenylsulfinyl,    phenylsulfonyl or phenoxy, it being possible for the phenyl groups    in turn to be substituted by C₁-C₃alkyl, C₁-C₃haloalkyl,    C₁-C₃alkoxy, C₁-C₃haloalkoxy, halogen, cyano or by nitro;-   Ra₄ is hydrogen, C₁-C₆alkyl, hydroxy, C₁-C₆alkoxy, C₁-C₆haloalkoxy,    C₃-C₆alkenyloxy, C₃-C₆haloalkenyloxy, C₃-C₆alkynyloxy,    C₁-C₄alkylcarbonyloxy, C₁-C₄alkylsulfonyloxy, phenylsulfonyloxy,    C₁-C₄alkylthio, C₁-C₄alkylsulfinyl, C₁-C₄alkylsulfonyl,    C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, C₁-C₄alkoxycarbonyl,    C₁-C₄haloalkyl, formyl, cyano, halogen, phenyl or phenoxy; it being    possible for the phenyl-containing groups in turn to be substituted    by C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy,    halogen, cyano or by nitro; or-   Ra₄ is a three- to ten-membered monocyclic or with Ra₃ or Ra₅    annellated bicyclic ring system which may contain from 1 to 4 hetero    atoms selected from nitrogen, oxygen and sulfur, the ring system,    unless it is annellated, being bonded to the group Q₁ or Q₂ either    directly or by way of a C₁-C₄alkylene, C₁-C₄alkenylene or    C₂-C₄alkynylene bridge which may be interrupted by oxygen,    —N(C₁-C₄alkyl)-, sulfur, sulfinyl, sulfonyl or by carbonyl; and the    ring system may contain not more than 2 oxygen atoms and not more    than two sulfur atoms, and the ring system may in turn may be mono-,    di- or tri-substituted by C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl,    C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₁-C₆alkoxy,    C₁-C₆haloalkoxy, C₃-C₆alkenyloxy, C₃-C₆alkynyloxy, C₁-C₆alkylthio,    C₁-C₆haloalkylthio, C₃-C₆alkenylthio, C₃-C₆haloalkenylthio,    C₃-C₆alkynylthio, C₁-C₄alkoxy-C₁-C₂alkylthio,    C₁-C₄alkylcarbonyl-C₁-C₂alkylthio,    C₁-C₄alkoxycarbonyl-C₁-C₂alkylthio, cyano-C₁-C₄alkylthio,    C₁-C₆alksulfinyl, C₁-C₆haloalkylsulfinyl, C₁-C₆alkylsulfonyl,    C₁-C₆haloalkylsulfonyl, aminosulfonyl, C₁-C₄alkylaminosulfonyl,    di(C₁-C₄alkyl)aminosulfonyl, amino, C₁-C₄alkylamino,    di(C₁-C₄alkyl)amino, halogen, cyano, nitro, phenyl and/or by    benzylthio; it being possible for phenyl and benzylthio in turn to    be substituted on the phenyl ring by C₁-C₃alkyl, C₁-C3haloalkyl,    C₁-C₃alkoxy, C₁-C₃haloalkoxy, halogen, cyano or by nitro, and    substituents on the nitrogen in the heterocyclic ring are other than    halogen;-   Ra₅ is hydrogen, C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl,    C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₃-C₆cycloalkyl,    C₁-C₆alkoxy, C₁-C₆haloalkoxy, C₁-C₆alkylthio, C₁-C₆alkylsulfinyl,    C₁-C₆alkylsulfonyl, C₁-C₆haloalkylthio, C₁-C₆haloalkylsulfinyl,    C₁-C₆haloalkylsulfonyl, C₁-C₆alkylsulfonyloxy, hydroxy, mercapto,    amino, C₁-C₆alkylamino, di(C₁-C₆alkyl)amino,    C₁-C₄alkylsulfonylamino, C₁-C₄alkylsulfonyl-N(C₁-C₄alkyl)-,    C₁-C₆alkylaminosulfonyl, di(C₁-C₆alkyl)aminosulfonyl, cyano,    halogen, C₁-C₄alkoxy-C₁-C₄alkyl, C₁-C₄alkylthio-C ₁-C₄alkyl,    C₁-C₄alkylsulfinyl-C₁-C₄alkyl, C₁-C₄alkylsulfonyl-C₁-C₄alkyl,    triazolyl, phenyl, phenylthio, phenylsulfinyl, phenylsulfonyl or    phenoxy; it being possible for the phenyl-containing groups to be    substituted by C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy,    C₁-C₃haloalkoxy, halogen, cyano or by nitro; and agronomically    acceptable salts/N-oxides/isomers/enantiomers of those compounds.

The alkyl groups appearing in the above substituent definitions may bestraight-chain or branched and are, for example, methyl, ethyl,n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl. Alkoxy,alkenyl and alkynyl radicals are derived from the mentioned alkylradicals. The alkenyl and alkynyl groups may be mono- orpoly-unsaturated. Alkoxy is, for example, methoxy, ethoxy, propoxy,isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy.Alkoxycarbonyl is, for example, methoxycarbonyl, ethoxycarbonyl,propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl,isobutoxycarbonyl, sec-butoxycarbonyl or tert-butoxycarbonyl; preferablymethoxycarbonyl or ethoxycarbonyl.

Halogen is generally fluorine, chlorine, bromine or iodine. The sameapplies also to halogen in conjunction with other meanings, such ashaloalkyl or halophenyl. Haloalkyl groups having a chain length of from1 to 6 carbon atoms are, for example, fluoromethyl, difluoromethyl,chlorodifluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl,trichloromethyl, 2,2,2-trifluoroethyl, 1-fluoroethyl, 2-fluoroethyl,2-chloroethyl, 2-fluoroprop-2-yl, pentafluoroethyl,1,1-difluoro-2,2,2-trichloroethyl, 2,2,3,3-tetrafluoroethyl and2,2,2-trichloroethyl, pentafluoroethyl, heptafluoro-n-propyl andperfluoro-n-hexyl.

Alkenyl and alkynyl groups may be mono- or poly-unsaturated, so thatalkyl, alkenyl and alkynyl chains having one or more double or triplebonds are also included. Alkenyl is, for example, vinyl, allyl,isobuten-3-yl, CH₂═CH—CH₂—CH═CH—, CH₂═CH—CH₂—CH₂—CH═CH— orCH₃—CH═CH—CH₂—CH═CH—. A preferred alkynyl is, for example, propargyl,and a preferred allenyl is CH₂═C═CH₂—.

An alkylene chain may also be substituted by one or more C₁-C₃alkylgroups, especially by methyl groups. Such alkylene chains and alkylenegroups are preferably unsubstituted. The same applies also to all groupscontaining C₃-C₆cycloalkyl, C₃-C₅oxacycloalkyl, C₃-C₅thiacycloalkyl,C₃-C₄dioxacycloalkyl, C₃-C₄dithiacycloalkyl or C₃-C₄oxathiacycloalkyl,which occur, for example, also as part of oxygen- and sulfur-containingheterocyclic ring systems of the radicals Ra₁ and Ra₂.

A C₁-C₄alkylene, C₁-C₄alkenylene or C₂-C₄alkynylene chain which may beinterrupted by oxygen, —N(C₁-C₄alkyl)-, sulfur, sulfinyl or by sulfonyl,or in X₂ or X₆ in the meaning of a C₁-C₆alkylene, C₃-C₆alkenylene orC₃-C₆alkynylene chain which may be mono- or poly-substituted by halogenor by X₄ or X₈, and wherein the unsaturated bonds of the chain are notbonded directly to the substituent X₁ or X₅, is to be understood asbeing, for example —CH₂—, —CH₂CH₂—, —CH₂CH₂CH₂—, —CH₂CH₂CH₂CH₂—,—CH(CH₃)—, —CH₂CH(CH₃)—, —CH₂CH(CH₃)CH₂—, —CH₂CH(Cl)CH₂—,—CH₂CH(OCH₃)CH₂—, —CH₂O—, —OCH₂—, —CH₂OCH₂—, —OCH₂CH₂—, —OCH₂CH₂CH₂—,—CH₂OCH₂CH₂—, —CH₂OCH(CH₃)CH₂—, SCH₂—, —SCH₂CH₂—, —SCH₂CH₂CH₂—, —CH₂S—,—CH₂SCH₂—, —CH₂S(O)CH₂—, —CH₂SO₂CH₂—, —CH₂SCH₂CH₂—, —CH₂S(O)CH₂CH₂—,—CH₂SO₂CH₂CH₂—, —CH₂SO₂NH—, —CH₂N(CH₃)SO₂CH₂CH₂—, —N(SO₂Me)CH₂CH₂—,—CH₂C(O)NH— or —CH₂NHC(O)CH₂—. A C₂-C₄alkenylene chain which may beinterrupted by oxygen is accordingly to be understood as being, forexample, —CH═CH—CH₂—, —CH═CH—CH₂CH₂— or —CH═CHCH₂OCH₂—, and aC₂-C₄alkynlene chain which may be interrupted by oxygen is to beunderstood as being, for example, —C≡C—, —C≡CCH₂—, —C≡CCH₂O—,—C≡CCH₂OCH₂— or —OC≡CCH₂—.

A three- to ten-membered mono- or bi-cyclic ring system Ra₁ or Ra₂,which may be interrupted once or up to three times selected from oxygen,sulfur, S(O), SO₂, N(Ra₆), carbonyl and C(═NORa₇) and which is bonded tothe carbon atom of the substituent A₁ or to the group Q₁ or Q₂ eitherdirectly or by way of a C₁-C₄alkylene, C₁-C₄alkenylene orC₂-C₄alkynylene bridge which may be interrupted by oxygen,—N(C₁-C₄alkyl)-, sulfur, sulfinyl or by sulfonyl, is to be understood asbeing, for example, 1-methyl-1H-pyrazol-3-yl, 1-ethyl-1H-pyrazol-3-yl,1-propyl-1H-pyrazol-3-yl, 1H-pyrazol-3-yl, 1,5-dimethyl-1H-pyrazol-3-yl,4-chloro-1-methyl-1H-pyrazol-3-yl, 1H-pyrazol-1-yl,3-methyl-1H-pyrazol-1-yl, 3,5-dimethyl-1H-pyrazol-1-yl, 3-isoxazolyl,5-methyl-3-isoxazolyl, 3-methyl-5-isoxazolyl, 5-isoxazolyl,1H-pyrrol-2-yl, 1-methyl-1H-pyrrol-2-yl, 1H-pyrrol-1-yl,1-methyl-1H-pyrrol-3-yl, 2-furyl, 5-methyl-2-furyl, 3-furyl,5-methyl-2-thienyl, 2-thienyl, 3-thienyl, 1-methyl-1H-imidazol-2-yl,1H-imidazol-2-yl, 1-methyl-1H-imidazol-4-yl, 1-methyl-1H-imidazol-5-yl,4-methyl-2-oxazolyl, 5-methyl-2-oxazolyl, 2-oxazolyl,2-methyl-5-oxazolyl, 2-methyl-4-oxazolyl, 4-methyl-2-thiazolyl,5-methyl-2-thiazolyl, 2-thiazolyl, 2-methyl-5-thiazolyl,2-methyl-4-thiazolyl, 3-methyl-4-isothiazolyl, 3-methyl-5-isothiazolyl,5-methyl-3-isothiazolyl, 1-methyl-1H-1,2,3-triazol-4-yl,2-methyl-2H-1,2,3-triazol-4-yl, 4-methyl-2H-1,2,3-triazol-2-yl,1-methyl-1H-1,2,4-triazol-3-yl, 1,5-dimethyl-1H-1,2,4-triazol-3-yl,3-methyl-1H-1,2,4-triazol-1-yl, 5-methyl-1H-1,24-triazol-1-yl,4,5-dimethyl-4H-1,2,4-triazol-3-yl, 4-methyl-4H-1,2,4-triazol-3-yl,4H-1,2,4-triazol-4-yl, 5-methyl-1,2,3-oxadiazol-4-yl,1,2,3-oxadiazol-4-yl, 3-methyl-1,2,4-oxadiazol-5-yl,5-methyl-1,2,4-oxadiazol-3-yl, 4-methyl-3-furazanyl, 3-furazanyl,5-methyl-1,2,4-oxadiazol-2-yl, 5-methyl-1,2,3-thiadiazol-4-yl,1,2,3-thiadiazol-4-yl, 3-methyl-1,2,4-thiadiazol-5-yl,5-methyl-1,2,4-thiadiazol-3-yl, 4-methyl-1,2,5-thiadiazol-3-yl,5-methyl-1,3,4-thiadiazol-2-yl, 1-methyl-1H-tetrazol-5-yl,1H-tetrazol-5-yl, 5-methyl-1H-tetrazol-1-yl, 2-methyl-2H-tetrazol-5-yl,2-ethyl-2H-tetrazol-5-yl, 5-methyl-2H-tetrazol-2-yl, 2H-tetrazol-2-yl,2-pyridyl, 6-methyl-2-pyridiyl, 4-pyridyl, 3-pyridyl,6-methyl-3-pyridazinyl, 5-methyl-3-pyridazinyl, 3-pyridazinyl,4,6-dimethyl-2-pyrimidinyl, 4-methyl-2-pyrimidinyl, 2-pyrimidinyl,2-methyl-4-pyrimidinyl, 2-chloro-4-pyrimidinyl,2,6-dimethyl-4-pyrimidinyl, 4-pyrimidinyl, 2-methyl-5-pyrimidinyl,6-methyl-2-pyrazinyl, 2-pyrazinyl, 4,6-dimethyl-1,3,5-triazin-2-yl,4,6-dichloro-1,3,5-triazin-2-yl, 1,3,5-triazin-2-yl,4-methyl-1,3,5-triazin-2-yl, 3-methyl-1,2,4-triazin-5-yl,3-methyl-1,2,4-triazin-6-yl,

wherein each R₂₆ is methyl, each R₂₇ independently is hydrogen,C₁-C₃alkyl, C₁-C₃alkoxy, C₁-C₃alkylthio or trifluoromethyl, and X₉ isoxygen or sulfur.

A further annellated (fused-on), monocyclic or bicyclic ring systemwhich is formed, for example, by two adjacent substituents Ra₁ and Ra₂or Ra₁ and Ra₅ and which is interrupted once or up to three timesselected from oxygen, sulfur, S(O), SO₂, —N(Ra₆)—, carbonyl andC(═NORa₇) and which may be additionally substituted by one or moresubstituents is to be understood as being, for example, an annellated,bidentate ring system of formula

wherein especially R₄₆ is hydrogen, halogen, C₁-C₄alkyl, C₁-C₄haloalkyl,C₁-C₄alkoxy or C₁-C₄alkylthio; R₄₇ is hydrogen, halogen, C₁-C₄alkyl orC₁-C₄alkoxy; R₅₀, R₅₁, R₅₂, R₅₃, R₅₄, R₅₅, R₅₆, R₅₇, R₅₈ and R₅₉ areeach independently of the others hydrogen C₁-C₄alkyl; and X₁₀ is oxygenor NOR₅₉.

A heteroaryl group Y substituted at least in the ortho position is to beunderstood as being especially a 5- or 6-membered aromatic heteroarylgroup as defined hereinbefore which is, in addition, substituted once orup to three times by substituents selected from the meanings of Ra₁,Ra₂, Ra₃ and Ra₄ and Ra₅ at the nitrogen and/or at the carbon atoms.

Using the process according to the invention it is possible, especiallyadvantageously, to prepare the cyclohexanedione herbicides described inWO 00/15615, WO 00/37437, WO 01/66522 and WO 01/94339.

Compounds of formula I that are highly suitable for preparation usingthe process according to the invention are those wherein

-   R₁ and R₂ are hydrogen;-   Q is Q₁, wherein A₄ is CRa₁ or N—(O)_(p);-   p is 0;-   Ra₁ is hydrogen, C₁-C₆alkyl, hydroxy, C₁-C₆alkoxy, C₁-C₆haloalkoxy,    C₃-C₆alkenyloxy, C₃-C₆haloalkenyloxy, C₃-C₆alkynyloxy,    C₁-C₄alkoxy-C₁-C₂alkoxy, C₁-C₄alkoxy-C₁-C₂alkoxy-C₁-C₂alkoxy,    (C₃-C₆cycloalkyl)-C₁-C₂alkoxy, (1,3-dioxolan-2-yl)-C₁-C₂alkoxy,    (tetrahydro-furan-2-yl)-C₁-C₂alkoxy, (tetrahydro-furan-3-yl)oxy,    (oxetan-3-yl)oxy, (C₃-C₆cycloalkyl)oxy, C₁-C₄alkylsulfonyloxy,    C₁-C₄alkylthio, C1-C₄alkylsulfonyl, C₁-C₄alkylamino,    di(C₁-C₄alkyl)amino, C₁-C₂alkoxyethylamino,    C₁-C₂alkoxyethyl-(N-methyl)amino, morpholino,    C₁-C₄alkylcarbonylaminoethoxy, C₁-C₄alkoxycarbonyl, hydroxymethyl,    C₁-C₆alkoxymethyl, C₁-C₆haloalkoxymethyl, C₃-C₆alkenyloxymethyl,    C₃-C₆haloalkenyloxymethyl, C₃-C₆alkynyloxymethyl,    C₁-C₄alkoxy-C₁-C₂alkoxymethyl, (C₃-C₆cycloalkyl)methoxymethyl,    (1,3-dioxolan-2-yl) methoxymethyl,    (tetrahydro-furan-2-yl)methoxymethyl,    (tetrahydro-furan-3-yl)oxymethyl, (oxetan-3-yl)oxymethyl,    (C₃-C₆cycloalkyl)oxymethyl, C₁-C₄alkylcarbonylamino-C₁-C₂alkoxy,    C₁-C₄haloalkyl, cyano, halogen, phenyl or benzyloxy, it being    possible for a phenyl-containing group in turn to be substituted by    C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, halogen,    cyano or by nitro;-   Ra₂ is C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl,    C₂-C₆alkynyl, C₃-C₆cycloalkyl, halo- or    C₁-C₂alkoxymethyl-substituted C₃-C₆cycloalkyl, C₁-C₆alkoxy,    C₃-C₆alkenyloxy, C₃-C₆alkynyloxy, C₁-C₆haloalkoxy,    C₃-C₆haloalkenyloxy, C₁-C₄alkoxy-C₁-C₄alkoxy-C₁-C₄alkoxy,    C₁-C₄alkylthio-C₁-C₄alkoxy, C₁-C₄alkylsulfinyl-C₁-C₄alkoxy,    C₁-C₄alkylsulfonyl-C₁-C₄alkoxy, C₁-C₄alkoxycarbonyl-C₁-C₄alkoxy,    C₁-C₆alkylthio, C₁-C₆alkylsulfinyl, C₁-C₆alkylsulfonyl,    C₁-C₆haloalkylthio, C₁-C₆haloalkylsulfinyl, C₁-C₆haloalkylsulfonyl,    C₁-C₆alkylaminosulfonyl, di(C₁-C₆alkyl)aminosulfonyl,    C₁-C₄alkylsulfonyloxy, C₁-C₄haloalkylsulfonyloxy,    C₁-C₄alkylsulfonylamino, C₁-C₄alkylsulfonyl-N(C₁-C₄-alkyl), cyano,    halogen, hydroxy-C₁-C₄alkyl, C₁-C₄alkoxy-C₁-C₄alkyl,    C₁-C₄alkylthio-C₁-C₄alkyl, C₁-C₄alkylsulfinyl-C₁-C₄alkyl,    C₁-C₄alkylsulfonyl-C₁-C₄alkyl, cyano-C₁-C₄alkyl,    C₁-C₆alkylcarbonyloxy-C₁-C₄alkyl, C₁-C₄alkoxycarbonyl-C₁-C₄alkyl,    C₁-C₄alkoxycarbonyloxy-C₁-C₄alkyl, phenoxy-C₁-C₄alkyl,    benzyloxy-C₁-C₄alkyl, benzoyloxy-C₁-C₄alkyl, benzyloxy, benzylthio,    phenoxy or phenylthio, it being possible for the phenyl-containing    groups in turn to be substituted by C₁-C₃alkyl, C₁-C₃haloalkyl,    C₁-C₃alkoxy, C₁-C₃haloalkoxy, halogen, cyano or by nitro; or-   Ra₂ is the group -X₁-X₃ or the group -X₂-X₁-X₃, wherein X₁, X₂ and    X₃ are as defined hereinbefore; or-   Ra₃ is hydrogen; or-   Ra₄ is hydrogen or methyl; or-   Ra₅ is C₁-C₆haloalkyl, C₂-C₆haloalkenyl, C₁-C₆alkoxy,    C₁-C₆haloalkoxy, C₁-C₆alkylthio, C₁-C₆alkylsulfinyl,    C₁-C₆alkylsulfonyl, C₁-C₆haloalkylthio, C₁-C₆haloalkylsulfinyl,    C₁-C₆haloalkylsulfonyl, C₁-C₆alkylsulfonyloxy,    C₁-C₄alkylaminosulfonyl, di(C₁-C₄alkyl)aminosulfonyl,    C₁-C₄alkylsulfonylamino, C₁-C₄alkylsulfonyl-N(C₁-C₄alkyl)-, cyano,    halogen, C₁-C₄alkoxymethyl, C₁-C₄alkylthiomethyl,    C₁-C₄alkylsulfinylmethyl, C₁-C₄alkylsulfonylmethyl or 1H-1,2,    4-triazol-1-yl.

Compounds of formula I that are especially highly suitable forpreparation using the process according to the invention are thosewherein

-   R₂ and R₅ together are ethylene;-   R₁ and R₆ are hydrogen;-   A₂ is C(R₃R₄)_(n), wherein R₃ and R₄ are hydrogen and n is 1.

The process according to the invention is explained in greater detail bythe following Examples.

Reaction Step a):

A preferred bromination agent is oxalyl bromide. A suitable chlorinationagent is thionyl chloride, oxalyl chloride or phosgene. The reaction maybe carried out in the presence of a base such as, for example, atertiary amine or heterocyclic amine, or an inorganic carbonate orhydrogen carbonate. The reaction may furthermore be carried out withoutthe addition of base in the presence of a catalytic amount of a tertiaryamide such as, for example, dimethylformamide. The reaction of thecompound of formula II with the compound of formula III is carried outin the presence of a base such as, for example, a tertiary amine orheterocyclic amine, or an inorganic carbonate and a catalytic amount ofa tertiary amide such as, for example, dimethylformamide, R₉ preferablybeing methyl. Reaction Step a) may be carried out at temperatures from0° C. to 100° C.

Suitable solvents are ethers, hydrocarbons or chlorinated hydrocarbons.

Compounds of formula 11 are known; they are commercially available insome cases or can be prepared by known methods.

The intermediates of formula IV

wherein A₁, A₂ and A₃ are as defined for formula I and Z₁ is chlorine,bromine or OSO₂R₉, R₉ being as defined for formula III, are novel andwere developed specifically for the present process, and the presentinvention accordingly also relates thereto.

Especially preferred intermediates are the compounds of formulae IVa andIVb

wherein Z₂ is chlorine, bromine or OSO₂R₉, R₉ being as defined forformula III but preferably being methyl.Reaction Step b):

Reaction Step b) is carried out in the absence of water and in thepresence of a base, for example a tertiary amine, preferablytriethylamine or diisopropylethylamine. The reaction is preferablycarried out in the presence of a solvent such as a hydrocarbon,acetonitrile, ether or dipolar aprotic solvent. When Z₁ is OSO₂R₉, thereaction is preferably carried out in chlorobenzene, toluene,acetonitrile or tetrahydrofuran. For activation of the leaving group Z₁,the presence of a catalyst such as, for example, a Lewis acid such asZnCl₂ or AgClO₄ is advantageous. When Z₁ is chlorine or bromine, thereaction is preferably carried out in the presence of acetonitrile,toluene, xylene or chlorobenzene as solvent. When Z₁ is OSO₂R₉, thereaction temperatures are from 0° C. to 150° C., preferably from 0° C.to 100° C. When Z₁ is chlorine or bromine, the reaction is preferablycarried out at temperatures of from 80° C. to 130° C.

Reaction Step c):

In an especially preferred embodiment of the process according to theinvention, the reaction according to Reaction Step c) is carried outwithout isolation of intermediates, that is to say the compound offormula VI obtained according to Reaction Step b) is treated in situwith cyanide ions in the presence of a base.

The cyanide ions are preferably used in amounts of from 0.01% to 15%.The reaction is preferably carried out at a temperature of from 50° C.to 150° C., especially at from 50° C. to 100° C., in the absence ofwater and in the presence of a base, for example from 0.1 to 2.5equivalents of triethylamine, or Hünig's base.

A suitable cyanide ion source is, for example, sodium cyanide, potassiumcyanide, copper(I) cyanide, acetone cyanohydrin or trimethylsilylcyanide, preferably potassium cyanide. Suitable solvents for ReactionStep c) are, for example, hydrocarbons, acetonitriles, ethers,chlorinated hydrocarbons and dipolar aprotic solvents. Such enol esterrearrangements are described, for example, in EP-A-0 186 117.

In a very especially preferred embodiment of the process according tothe invention, Reaction Steps a), b) and c) are carried out withoutisolation of intermediates, in the form of a one-pot reaction. Thepossibility of carrying out the process according to the invention in aone-pot reaction constitutes a considerable advantage especially forlarge-scale application.

The process according to the invention will be explained in greaterdetail in the following Preparation Examples:

EXAMPLE P1 Preparation of 3-bromobicyclo[3.2.1]oct-2-en-1-one

To a solution of 5 g (34.4 mmol) of bicyclo[3.2.1]octane-2,4-dione(preparation in accordance with JP 10265441 A2) in 50 ml ofdichloromethane there are added, in succession, with stirring, 0.05 mlof dimethylformamide and then, over the course of 15 minutes, 8.9 g(41.3 mmol) of oxalyl bromide in portions, during which gas is evolved.The exothermic reaction is controlled using a water bath. The resultinglight-brown solution is stirred for one hour at ambient temperature. Thereaction mixture is then washed with 50 ml of 1M sodium hydrogencarbonate solution, a high degree of foaming being observed, and is thendried using magnesium sulfate. After removal of the solvent in vacuo,4.8 g (56% of theory) of 3-bromobicyclo[3.2.1]oct-2-en-1-one areobtained in the form of a dark-brown oil.

MS: 202 (M⁺ ⁸¹Br isotope), 200 (M⁺ ⁷⁹Br isotope), 161, 159, 133, 131,121, 91, 77, 65, 51, 39

¹H NMR (CDCl₃): 1.60-1.70 (m, 2H), 1.85-1.95 (m, 1H), 1.95-2.05 (m, 1H),2.10-2.20 (m, 2H), 2.95 (m, 1H), 3.20 (m, 1H), 6.20 (s, 1H).

EXAMPLE P2 3-Chlorobicyclo[3.2.1]oct-2-en-1-one

To a solution of 4.8 g (32.8 mmol) of bicyclo[3.2.1]octane-2,4-dione in50 ml of dichloromethane there are added, in succession, with stirring,0.05 ml of dimethylformamide and then, over the course of 30 minutes, 5g (39.4 mmol) of oxalyl chloride in portions, during which gas isevolved. The exothermic reaction is controlled using a water bath. Theresulting red-brown solution is stirred for 30 minutes at ambienttemperature. The reaction mixture is divided into two equal portions.One portion of the reaction mixture is then washed with 50 ml of 1Msodium hydrogen carbonate solution, a high degree of foaming beingobserved. After removal of the solvent in vacuo, 1.9 g (70% of theory)of 3-chlorobicyclo[3.2.1]oct-2-en-1-one are obtained in the form of abrown oil.

MS: 158 (M⁺ ³⁷Cl isotope), 156 (M⁺ ³⁵Cl isotope), 117, 115, 91, 87, 77,65, 51, 39

¹H NMR (CDCl₃): 1.60-1.70 (m, 2H), 1.80-1.95 (m, 1H), 2.00-2.10 (m, 1H),2.15-2.25 (m, 2H), 2.95 (m, 1H), 3.05 (m, 1H), 6.00 (s, 1H)

EXAMPLE P3 Preparation of4-oxo-bicyclo[3.2.1]oct-2-en-2-yl-methanesulfonic acid ester

13.82 g (100 mmol) of bicyclo[3.2.1]octane-2,4-dione, 11.46 g (100 mmol)of methanesulfonyl chloride and 15.18 g (150 mmol) of triethylamine areheated in 100 ml of chloroform at a temperature of from 60 to 65° C.with stirring for 24 hours. 15.3 g of4-oxo-bicyclo-[3.2.1]oct-2-en-2-yl-methanesulfonic acid ester in theform of a brown, gum-like product are obtained, which can be used forthe next Reaction Step without further purification.

¹H NMR (CDCl₃): 1.6-1.75 (m, 2H), 1.9-2.2 (m, 4H), 2.9-3.0 (m, 2H,bridgehead), 3.25 (s, 3H, CH₃SO₃—), 5.8 (s, 1H, vinyl).

EXAMPLE P4 Preparation of2-phenylcarbonyloxy-4-oxo-bicyclo[3.2.1]oct-2-ene

2.165 g (10 mmol) of 4-oxo-bicyclo[3.2.1]oct-2-en-2-yl-methanesulfonicacid ester (Preparation Example P3), 1.34 g (11 mmol) of benzoic acidand 1.52 g (15 mmol) of triethylamine in 20 ml of chlorobenzene areheated with stirring for 8 hours. The cooled reaction mixture is thenwashed with 5% aqueous sulfuric acid and 5% aqueous sodium hydroxide.The organic phase is dried over sodium sulfate and concentrated todryness by evaporation in vacuo. 2.99 g of2-phenylcarbonyloxy-4-oxo-bicyclo[3.2.1]oct-2-ene are obtained in theform of a brown oil.

¹H NMR (CDCl₃): 1.65-1.8 (m, 2H), 2.0-2.4 (m, 4H), 2.95-3.1 (m, 2H,bridgehead), 5.85 (s, 1H, vinyl), 6.95-7.05 (m, 2H, aryl), 7.1-7.2 (m,1H, aryl), 8.05-8.15 (m, 2H, aryl).

EXAMPLE P5 Preparation of3-(2-nitro-4-methylsulfonyl-phenylcarbonyloxy)-cyclohex-2-en-1-one

To a mixture of 157 mg (1.15 mmol) of 3-chlorocyclohex-2-en-1-one(prepared as described in Synthesis (1974), (1), 47-8), 16 mg (0.12mmol) of ZnCl₂, 297 mg (1.15 mmol) of 2-nitro-4-methylsulfonybenzoicacid and 3 ml of anhydrous acetonitrile there are added dropwise, undera nitrogen atmosphere, over the course of 15 minutes, 166 mg (1.27 mmol)of diisopropylethylamine. A further 2 ml of acetonitrile are then addedand, with stirring, the reaction mixture is maintained at a temperatureof 45° C. for 18 hours in an oil bath. The reaction mixture is thenheated up again and maintained at reflux temperature for 40 hours.

The reaction mixture is then brought to ambient temperature and thesolvent is removed in vacuo. 25 ml of dichloromethane and 0.35 g of 36%hydrochloric acid in 5 ml of water are then added and the phases areseparated. The organic phase is washed twice with 10 ml of water, driedusing magnesium sulfate and concentrated in vacuo. 197 mg of3-(2-nitro-4-methylsulfonyl-phenylcarbonyloxy)-cyclohex-2-en-1-one areobtained in the form of a brown oil.

¹H NMR (CDCl₃): 2.10-2.20 (m, 2H), 2.45-2.50 (m, 2H), 2.70-2.75 (m, 2H),3.20 (s, 3H, CH ₃SO₂), 6.10 (s, 1H, C═CH), 8.00 (d, 1H, ar. H), 8.35 (d,1H, ar. H), 8.65 (s, 1H, ar. H).

EXAMPLE P6 Preparation of3-(2-methoxyethoxymethyl-6-trifluoromethyl-pyridin-3-ylcarbonyloxy)-cyclohex-2-en-1-one

To a mixture of 157 mg (1.15 mmol) of 3-chlorocyclohex-2-en-1-one, 16 mg(0.12 mmol) of ZnCl₂, 324 mg (1.15 mmol) of2-methoxyethoxymethyl-6-trifluoromethylnicotinic acid (preparationdescribed in WO 2001094339) and 2 ml of toluene there are addeddropwise, under a nitrogen atmosphere, over the course of 15 minutes,166 mg (1.27 mmol) of diisopropylethylamine. A further 2 ml of tolueneare then added and, with stirring, the reaction mixture is maintainedunder moderate reflux for 18 hours in an oil bath. The reaction mixtureis then brought to ambient temperature and 30 ml of dichloromethane and20 ml of water are added. The organic phase is separated off and washedtwice with 0.1M hydrochloric acid (20 ml) and twice with water (10 ml).After drying using magnesium sulfate and concentration in vacuo, 226 mgof3-(2-methoxyethoxymethyl-6-trifluoromethyl-pyridin-3-ylcarbonyloxy)-cyclohex-2-en-1-oneare obtained in the form of an orange-brown oil.

MS: 373 (M⁺), 354, 328, 262, 230, 202, 187, 159, 139, 109, 95, 59, 45.

¹H NMR (CDCl₃): 2.10-2.20 (m, 2H), 2.45-2.50 (m, 2H), 2.70-2.75 (m, 2H),3.35 (s, 3H, CH ₃O), 3.50 (CH₂CH ₂O), 3.70 (OCH ₂CH₂), 5.00 (s, 2H, ar.CH ₂), 6.10 (s, 1, C═CH), 7.75 (d, 1H, ar. H), 8.30 (d, 1H, ar. H).

EXAMPLE P7 Preparation of4-(2-methoxyethoxymethyl-6-trifluoromethyl-pyridin-3-yl-carbonyloxy)-bicyclo[3.2.1]oct-3-en-2-one

A mixture of 200 mg (1.15 mmol) of 4-chlorobicyclo[3.2.1]oct-3-en-2-one,(Preparation Example P2) 16 mg (0.12 mmol) of ZnCl₂, 324 mg (1.15 mmol)of 2-methoxyethoxymethyl-6 -trifluoromethylnicotinic acid, 166 mg (1.27mmol) of diisopropylethylamine and 5 ml of toluene is stirred under anitrogen atmosphere at room temperature until a clear brown solutionhaving a white sediment is formed. The reaction mixture is thenmaintained under moderate reflux for 26 hours in an oil bath, withstirring. The reaction mixture is then cooled to ambient temperature and30 ml of dichloromethane are added. The solution is then washed twicewith water (20 ml each time) and then twice with 0.1M hydrochloric acid(20 ml each time) and again twice with water (15 ml each time). Afterdrying the organic solution using magnesium sulfate and concentrating invacuo, 284 mg of4-(2-methoxyethoxymethyl-6-trifluoromethyl-pyridin-3-ylcarbonyloxy)-bicyclo[3.2.1]oct-3-en-2-oneare obtained in the form of a brown oil.

MS: 399(M⁺), 380, 354, 262, 230, 204, 187, 159, 139, 121, 91.

¹H NMR (CDCl₃): 1.65-1.75 (m, 2H), 2.05-2.30 (m, 4H), 3.00 (br t, 1H),3.10 (br s, 1H), 3.35 (s, 3H, OCH ₃), 3.50 (m, 2H, CH₂CH ₂O), 3.70 (m,2H, OCH ₂CH₂), 5.00 (s, 2H, ar. CH ₂), 5.90 (s, 1H, C═CH), 7.75 (d, 1H,ar. H), 8.30 (d, 1H, ar. H).

EXAMPLE P8 Preparation of4-(4-chlorophenyl-carbonyloxy)-bicyclo[3.2.1]oct-3-en-2-one

A mixture of 500 mg of 4-chlorobicyclo[3.2.1]oct-3-en-2-one (PreparationExample P2), 440 mg of ZnCl₂, 400 mg of 4-chlorobenzoic acid, 1.05 g ofdiisopropylethylamine and 5 ml of toluene is stirred at room temperatureunder a nitrogen atmosphere at reflux temperature for 6 hours. Aftercooling, the reaction mixture is then diluted with dichloromethane andwashed with 5% aqueous sulfuric acid and 5% aqueous sodium hydroxide.After concentration of the organic phase to dryness by evaporation, 0.6g of 4-(4-chlorophenyl-carbonyloxy)-bicyclo[3.2.1]oct-3-en-2-one isobtained.

¹H NMR (CDCl₃): 1.65-1.8 (m, 2H), 2.0-2.4 (m, 4H), 2.95-3.1 (m, 2H,bridgehead), 5.85 (s, 1H, vinyl), 6.95-7.05 (m, 2H, aryl), 8.0-8.1 (m,2H, aryl).

EXAMPLE P9 Preparation of4-phenyl-carbonyloxy-bicyclo[3.2.1]oct-3-en-2-one

A mixture of 500 mg of 4-chlorobicyclo[3.2.1]oct-3-en-2-one (PreparationExample P2), 440 mg of ZnCl₂, 400 mg of 4-benzoic acid, 1.05 g ofdiisopropylethylamine and 5 ml of toluene is stirred at room temperatureunder a nitrogen atmosphere at reflux temperature for 8 hours. Aftercooling, the reaction mixture is then diluted with dichloromethane andwashed with 10% aqueous sulfuric acid. After concentration of theorganic phase to dryness by evaporation, 0.4 g of4-phenyl-carbonyloxy-bicyclo[3.2.1]oct-3-en-2-one is obtained.

¹H NMR (CDCl₃): 1.65-1.8 (m, 2H), 2.0-2.4 (m, 4H), 2.95-3.1 (m, 2H,bridgehead), 5.85 (s, 1H, vinyl), 6.95-7.05 (m, 2H, aryl), 7.1-7.2 (m,1H, aryl), 8.05-8.15 (m, 2H, aryl).

EXAMPLE P10 Preparation of4-(2-methoxyethoxymethyl-6-trifluoromethyl-pyridin-3-yl-carbonyloxy)-bicyclo[3.2.1]oct-3-en-2-one

A mixture of 27 g of a 6.2% solution of4-bromobicyclo[3.2.1]oct-3-en-2-one (Preparation Example P1) inchlorobenzene, 110 mg of ZnCl₂, 2.34 g of2-methoxyethoxymethyl-6-trifluoromethylnicotinic acid and 1.2 g ofHünig's base is stirred at room temperature under a nitrogen atmosphereuntil a dark-brown solution is formed. The reaction mixture is thenmaintained under moderate reflux for 19 hours in an oil bath, withstirring. The mixture is then divided into 2 portions. To one portionthere are added a further 1.12 g of2-methoxyethoxymethyl-6-trifluoromethylnicotinic acid, 0.06 g of ZnCl₂and 0.6 g of Hünig's base. The reaction mixture is then maintained undermoderate reflux for 12 hours in an oil bath, with stirring. The solutionis then washed twice with 0.1M hydrochloric acid (20 ml each time) andtwice with water (20 ml each time). After drying the organic solutionusing magnesium sulfate and concentrating in vacuo, 3.9 g of4-(2-methoxyethoxymethyl-6-trifluoromethyl-pyridin-3-ylcarbonyloxy)-bicyclo[3.2.1]oct-3-en-2-oneare obtained in the form of a brown oil.

MS: 399 (M⁺), 380, 354, 262, 230, 202, 187, 159, 139, 121, 91.

¹H NMR (CDCl₃): 1.65-1.75 (m, 2H), 2.05-2.30 (m, 4H), 3.00 (br t, 1H),3.10 (br s, 1H), 3.35 (s, 3H, OCH ₃), 3.50 (m, 2H, CH₂CH ₂O), 3.70 (m,2H, OCH ₂CH₂), 5.00 (s, 2H, ar. CH ₂), 5.90 (s, 1H, C═CH), 7.75 (d, 1H.ar. H), 8.30 (d, 1H. ar. H).

EXAMPLE P11 Preparation of4-hydroxy-3-(2-methoxyethoxymethyl-6-trifluoromethyl-pyridin-3-ylcarbonyl)-bicyclo[3.2.1]oct-3-en-2-one

To a mixture of 200 mg (1.15 mmol) of4-chlorobicyclo[3.2.1]oct-3-en-2-one (Preparation Example P2), 16 mg(0.12 mmol) of ZnCl₂, 324 mg (1.15 mmol) of2-methoxyethoxymethyl-6-trifluoromethylnicotinic acid and 2 ml oftoluene there are added dropwise, under a nitrogen atmosphere, over thecourse of 15 minutes, 166 mg (1.27 mmol) of diisopropylethylamine. Afurther 2 ml of toluene are then added and, with stirring, the reactionmixture is maintained under moderate reflux for 23 hours in an oil bath.The reaction mixture is then cooled to ambient temperature, and 4 ml ofacetonitrile, 2 drops of cyanohydrin, 465 mg of triethylamine and afurther 1 ml of acetonitrile are added. After drying the organic phaseusing magnesium sulfate and concentrating in vacuo, 452 mg of4-hydroxy-3-(2-methoxyethoxymethyl-6-trifluoromethyl-pyridin-3-ylcarbonyl)-bicyclo[3.2.1]oct-3-en-2-oneare obtained in the form of a viscous oil.

MS: 399 (M⁺), 380, 356, 340, 310, 282, 256, 228, 202, 174, 152, 128, 67,45.

¹H NMR (CDCl₃): 1.70-1.80 (m, 2H), 2.05-2.30 (m, 4H), 2.90 (br s, 1H),3.15 (br s, 1H), 3.30 (s, 3H, OCH ₃), 3.40 (m, 2H, CH₂CH ₂O), 3.50 (m,2H, OCH ₂), 4.75 (s, 2H, ar. CH ₂), 7.60 (s, 2H, ar. H).

1. A process for the preparation of a compound of formula I

wherein Y is an organic substituent which is so selected that the compound of formula I has a pK value of from 1 to 5; A₁ is CR₁R₂; A₂ is oxygen, C(O), SO₂ or (CR₃R₄)_(n); n is 1 or 2; A₃ is CR₅R₆; R₁, R₂, R₃, R₄, R₅ and R₆ are each independently of the others C₁-C₄alkyl which may be mono-, di- or tri-substituted by C₁-C₄alkoxy, halogen, hydroxy, cyano, hydroxycarbonyl, C₁-C₄alkoxycarbonyl, C₁-C₄alkylthio, C₁-C₄alkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄alkylcarbonyl, phenyl or by heteroaryl, it being possible for the phenyl and heteroaryl groups in turn to be mono-, di- or tri-substituted by C₁-C₄alkoxy, halogen, hydroxy, cyano, hydroxycarbonyl, C₁-C₄alkoxycarbonyl, C₁-C₄alkylsulfonyl or by C₁-C₄haloalkyl, the substituents on the nitrogen in the heterocyclic ring being other than halogen; and/or R₁, R₂, R₃, R₄, R₅ and R₆ are each independently of the others hydrogen, C₁-C₄alkoxy, halogen, hydroxy, cyano, hydroxycarbonyl, C₁-C₄alkoxycarbonyl, C₁-C₄alkylthio, C₁-C₄alkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄alkylcarbonyl, phenyl or heteroaryl, it being possible for the phenyl and heteroaryl groups in turn to be mono-, di- or tri-substituted by C₁-C₄alkoxy, halogen, hydroxy, cyano, hydroxycarbonyl, C₁-C₄alkoxycarbonyl, C₁-C₄alkylsulfonyl or by C₁-C₄haloalkyl, the substituents on the nitrogen in the heterocyclic ring being other than halogen; and/or R₁ and R₂ together form a 3- to 5-membered carbocyclic ring which may be substituted by C₁-C₄alkyl and/or interrupted by oxygen, sulfur, S(O), SO₂, OC(O), NR₇ or by C(O); and/or R₂ and R₄ together or R₂ and R₅ together form a C₁-C₃alkylene chain which may be interrupted by oxygen, sulfur, SO, SO₂, OC(O), NR₈ or by C(O); it being possible for that C₁-C₃alkylene chain in turn to be substituted by C₁-C₄alkyl; and R₇ and R₈ are each independently of the other C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkylsulfonyl, C₁-C₄alkylcarbonyl or C₁-C₄alkoxycarbonyl; in which process a) a compound of formula II

wherein A₁, A₂ and A₃ are as defined for formula I, is reacted, in the presence of a water-immiscible solvent, in the presence of a base or a catalytic amount of a tertiary amide, either with a chlorination or bromination agent or with a compound of formula III Cl—SO₂R₉  (III), wherein R₉ is C₁-C₄alkyl, C₁-C₄haloalkyl, phenyl or C₁-C₄alkyl-substituted phenyl, to form the compound of formula IV

wherein A₁, A₂ and A₃ are as defined for formula I and Z1 is chlorine, bromine or OSO₂R₉, R₉ being as defined hereinbefore; b) the compound of formula IV is converted, using a compound of formula V M⁺-O⁻—C(O)—Y  (V), wherein Y is as defined hereinbefore and M⁺ is the hydrogen cation or an alkali metal ion, alkaline earth metal ion or ammonium ion, into the compound of formula VI

and c) then the compound of formula VI is treated with a cyanide source in the presence of a base.
 2. Compounds of formulae IVa and IVb

wherein Z₂ is chlorine, bromine or OSO₂R₉, and R₉ is C₁-C₄alkyl, C₁-C₄haloalkyl, phenyl or C₁-C₄alkyl-substituted phenyl; wherein, if the compound has the formula IVb, then Z₂ is not chlorine or bromine and R₉ is not methyl, tolyl or CF₃.
 3. The compound according to claim 2, wherein the compound is of formula IVa and Z₂ is selected from the group consisting of chorine, bromine and —OSO₂CH₃. 